Institution
Yonsei University
Education•Seoul, South Korea•
About: Yonsei University is a education organization based out in Seoul, South Korea. It is known for research contribution in the topics: Population & Cancer. The organization has 50162 authors who have published 106172 publications receiving 2279044 citations. The organization is also known as: Yonsei.
Topics: Population, Cancer, Medicine, Thin film, Breast cancer
Papers published on a yearly basis
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TL;DR: Insight is provided into the evolutionary history for the PE and PPE gene families of the mycobacteria, linking the expansion of these families to the duplications of the ESAT-6 (esx) gene cluster regions, and showing that they are composed of subgroups with distinct evolutionary (and possibly functional) differences.
Abstract: The PE and PPE multigene families of Mycobacterium tuberculosis comprise about 10% of the coding potential of the genome. The function of the proteins encoded by these large gene families remains unknown, although they have been proposed to be involved in antigenic variation and disease pathogenesis. Interestingly, some members of the PE and PPE families are associated with the ESAT-6 (esx) gene cluster regions, which are regions of immunopathogenic importance, and encode a system dedicated to the secretion of members of the potent T-cell antigen ESAT-6 family. This study investigates the duplication characteristics of the PE and PPE gene families and their association with the ESAT-6 gene clusters, using a combination of phylogenetic analyses, DNA hybridization, and comparative genomics, in order to gain insight into their evolutionary history and distribution in the genus Mycobacterium. The results showed that the expansion of the PE and PPE gene families is linked to the duplications of the ESAT-6 gene clusters, and that members situated in and associated with the clusters represent the most ancestral copies of the two gene families. Furthermore, the emergence of the repeat protein PGRS and MPTR subfamilies is a recent evolutionary event, occurring at defined branching points in the evolution of the genus Mycobacterium. These gene subfamilies are thus present in multiple copies only in the members of the M. tuberculosis complex and close relatives. The study provides a complete analysis of all the PE and PPE genes found in the sequenced genomes of members of the genus Mycobacterium such as M. smegmatis, M. avium paratuberculosis, M. leprae, M. ulcerans, and M. tuberculosis. This work provides insight into the evolutionary history for the PE and PPE gene families of the mycobacteria, linking the expansion of these families to the duplications of the ESAT-6 (esx) gene cluster regions, and showing that they are composed of subgroups with distinct evolutionary (and possibly functional) differences.
401 citations
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TL;DR: Expression of the essential EMT inducer Snail1 is inhibited by miR-34 through a p53-dependent regulatory pathway.
Abstract: Snail1 is a zinc finger transcriptional repressor whose pathological expression has been linked to cancer cell epithelial–mesenchymal transition (EMT) programs and the induction of tissue-invasive activity, but pro-oncogenic events capable of regulating Snail1 activity remain largely uncharacterized. Herein, we demonstrate that p53 loss-of-function or mutation promotes cancer cell EMT by de-repressing Snail1 protein expression and activity. In the absence of wild-type p53 function, Snail1-dependent EMT is activated in colon, breast, and lung carcinoma cells as a consequence of a decrease in miRNA-34 levels, which suppress Snail1 activity by binding to highly conserved 3′ untranslated regions in Snail1 itself as well as those of key Snail1 regulatory molecules, including β-catenin, LEF1, and Axin2. Although p53 activity can impact cell cycle regulation, apoptosis, and DNA repair pathways, the EMT and invasion programs initiated by p53 loss of function or mutation are completely dependent on Snail1 expression. These results identify a new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs.
401 citations
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TL;DR: Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma.
Abstract: Summary Background Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. Methods In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m 2 on day 1 and oxaliplatin 100 mg/m 2 on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. Findings 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7–5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6–7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61–1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5–11·5] in the chemotherapy alone group and 9·5 months [7·6–11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69–1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3–4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7–7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1–4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53–1·00; p=0·049). Interpretation Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. Funding None.
401 citations
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Cornell University1, Harvard University2, The Chinese University of Hong Kong3, Sarah Cannon Research Institute4, University of California, San Francisco5, University of Bern6, Institut Gustave Roussy7, Yonsei University8, Ben-Gurion University of the Negev9, University of North Carolina at Chapel Hill10, Seoul National University11, Japanese Foundation for Cancer Research12, Sungkyunkwan University13, University of Chicago14, Tottori University15, Ohio State University16, University of California, San Diego17, New York University18, Okayama University19, University of Milan20, City of Hope National Medical Center21, Roswell Park Cancer Institute22, University of Cologne23, Peter MacCallum Cancer Centre24, University of Texas MD Anderson Cancer Center25
TL;DR: Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated.
Abstract: Background RET fusions are oncogenic drivers in 1 to 2% of non–small-cell lung cancers (NSCLCs). In patients with RET fusion–positive NSCLC, the efficacy and safety of selective RET inhibi...
400 citations
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TL;DR: Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and it is shown that the antioxidant function of Sesns is mediated through activation of NRF2 in a manner reliant on p62-dependent autophagic degradation of Keap 1.
398 citations
Authors
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Name | H-index | Papers | Citations |
---|---|---|---|
Younan Xia | 216 | 943 | 175757 |
Peer Bork | 206 | 697 | 245427 |
Ralph Weissleder | 184 | 1160 | 142508 |
Hyun-Chul Kim | 176 | 4076 | 183227 |
Gregory Y.H. Lip | 169 | 3159 | 171742 |
Yongsun Kim | 156 | 2588 | 145619 |
Jongmin Lee | 150 | 2257 | 134772 |
James M. Tiedje | 150 | 688 | 102287 |
Guanrong Chen | 141 | 1652 | 92218 |
Kazunori Kataoka | 138 | 908 | 70412 |
Herbert Y. Meltzer | 137 | 1148 | 81371 |
Peter M. Rothwell | 134 | 779 | 67382 |
Tae Jeong Kim | 132 | 1420 | 93959 |
Shih-Chang Lee | 128 | 787 | 61350 |
Ming-Hsuan Yang | 127 | 635 | 75091 |